Despite the increasing use of the newer “atypical” or second-generation antipsychotic agents to treat a spectrum of psychiatric disorders, including schizophrenia, bipolar disorder, major depression, PTSD and other anxiety disorders, we have relatively little data on the reproductive safety of these newer atypical agents.  In response to this deficit, the National Pregnancy Registry for Atypical Antipsychotics was created to evaluate the safety of atypical antipsychotic medications taken by women during pregnancy.  The first set of data from the registry has been published in this month’s issue of the American Journal of Psychiatry.

Pregnant women were recruited and prospectively followed during pregnancy and the postpartum period.  Eligible subjects were pregnant women ages 18–45.   As of December 2014, 487 women were enrolled; this included 353 women treated with second-generation antipsychotics and a comparison group of 134 women with histories of psychiatric morbidity who were not treated with antipsychotics.

Medical records were obtained for 82% of participants. A total of 303 women completed the study and were eligible for inclusion in the analysis.   The most commonly used second-generation antipsychotics in the exposed group were quetiapine, aripiprazole, and olanzapine.  Of 214 live births with first-trimester exposure to second-generation antipsychotics, three major malformations were confirmed. In the control group (N=89), one major malformation was confirmed. The absolute risk of major malformations was 1.4% for exposed infants and 1.1% for unexposed infants. The odds ratio for major malformations comparing exposed infants with unexposed infants was 1.25 (95% CI=0.13–12.19).

Based on the 214 cases of first-trimester exposure to second-generation antipsychotics, it would be reasonable to conclude that these agents as a class are not major teratogens. Ideally we would like to have greater numbers of exposed infants so that the analysis can assess the risks associated with exposure to specific antipsychotic medications.  Nonetheless the data are reassuring; although the confidence intervals are very wide and may change over the course of the study, it is unlikely that the risk will rise to that of major teratogens such as valproate or thalidomide.

When we advise our patients regarding the use of this class of medications, we cannot simply say that atypical antipsychotic are “safe”; instead, we must inform our patients of the limitations of the data we do have.  Based on the existing data, we cannot definitively rule out the possibility that there is some increase in risk for malformation.  Nor can we say much about some of the atypicals, such as lurasidone, which were underrepresented in the studies we do have.  Furthermore, we must take into consideration the indication for the usage of the antipsychotic medication.  For example, we would be more likely to maintain the use of an atypical antipsychotic in a patient with schizophrenia than in a patient who is using a low dose of an atypical agent to manage insomnia.

The National Pregnancy Registry for Atypical Antipsychotics continues to recruit pregnant women taking atypical antipsychotic medications.   CALL TOLL-FREE to learn more 1-866-961-2388 or fill out this Patient Interest Form to be contacted by our research coordinator. All information is kept strictly confidential.  Participation consists of three phone interviews.

Ruta Nonacs, MD PhD

Cohen LS, Viguera AC, McInerny KA, Freeman MP, et al. Reproductive Safety of Second-Generation Antipsychotics: Current Data From the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics. Am J Psychiatry 2015.

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